The long-term goal of this research is to understand better the regulation of plasma cholesterol and low density lipoprotein (LDL) concentrations. Elevated LDL is one of the factors associated with coronary heart disease and with familial hypercholesterolemia (FH). Our research will focus on lipoprotein receptors in tissues and cultured cells which might help to regulate plasma lipoproteins. Two receptors will be considered, a newly-found receptor of HepG2 liver cells, and the LDL receptor. The receptors will be purified from human cells and factors important in their control will be determined. FH is a disorder in which plasma LDL levels are too high because of deficient tissue LDL receptors. Recent work strongly suggests that LDL receptors are present in cells from FH patients, but are not adequately expressed. In order to understand FH better, the regulation of normal cell receptors will be studied and the finding compared to FH cells. In addition, polymorphism in LDL receptors will be studied in normal individuals and in patients with hyperlipidemias other than FH. Techniques used will include analysis of the binding and degradation of radioiodinated lipoproteins to cells, protein blotting with lipoproteins and antibodies used as detecting agents, protein purification and affinity chromatography, and the preparation of monoclonal antibodies.